Objectives of the proposed research are to understand interaction between macromolecules at crucial steps in biochemical systems. One goal is to obtain structural knowledge of the subunit structure assembly, organization, and changes in structure induced by ligand in a membrane containing an acetylcholine receptor from electric fish. Electron diffraction from ordered two-dimensional lattices of this and techniques for computer-optical reconstruction of stained and unstained electron micrographs were developed and will be used to obtain detailed information about a fundamental neurochemical element of synaptic transmission. The structure of alpha-Bungarotoxin, solved at 5 A resolution be pursued to high resolution and refined. The structure of cobrotoxin, which similarly blocks the acetylcholine receptor will be solved from a new crystal form obtained recently which diffracts to approximately 2.0 A resolution. The structures and different activities of these molecules will be compared in order to learn more about the complementary site on the receptor. Refinement of the structures of trypsin and trypsinogen will be completed (R equals 14% at 1. 5 A for trypsin), and attempts made to identify adequate solvent models. The structure analysis of human thrombin will be continued. Preliminary crystallization of a large extra loop (type III) tRNA, which diffracts to approximately 8 A and of tRNA charging enzyme complexes will be pursued in the hope of understanding tRNA plus charging enzyme recognition.